Time to Onset of Fluoxetine (Prozac) for Premature Ejaculation
Fluoxetine typically begins to show therapeutic effects for premature ejaculation within 1-2 weeks of daily treatment, with maximal efficacy achieved after 2-4 weeks of continuous use. 1
Evidence-Based Timeline
The American Urological Association recommends daily SSRI therapy as the most effective pharmacological approach for premature ejaculation, with fluoxetine 5-20 mg daily providing consistent and stronger ejaculatory delay compared to on-demand dosing. 1
Onset Window
Initial response: Clinical trials demonstrate that fluoxetine at doses of 5-10 mg/day produces significant increases in ejaculatory latency within the first treatment period, typically measured at 2-4 weeks. 2
Dose-dependent timing: Studies using fluoxetine 20 mg daily for 2 weeks followed by titration to 60 mg showed significant improvement in intravaginal ejaculation latency time within the 8-week study period, with benefits emerging in the early weeks. 3
Comparative data: Research directly comparing 90 mg weekly versus 20 mg daily fluoxetine found that after 3 months of treatment, mean ejaculatory latency time increased from 0.48-0.50 minutes at baseline to 3.37-3.57 minutes, indicating progressive improvement over weeks to months. 4
Dosing Strategy for Optimal Response
Start with fluoxetine 5-20 mg daily and maintain continuous (daily) dosing rather than on-demand use, as daily administration produces substantially greater and more consistent ejaculatory delay. 1
Key Dosing Considerations
Daily dosing is superior: Continuous daily dosing provides more consistent and stronger ejaculatory delay compared to situational (on-demand) dosing taken 3-4 hours before intercourse. 1
Titration approach: Begin at 5-20 mg daily and titrate based on response and tolerability, with some patients requiring up to 60-90 mg for optimal effect. 4, 3
Sexual side effects are dose-related: Higher doses increase efficacy but also increase the frequency of sexual side effects such as ejaculatory failure and decreased libido. 5
Important Clinical Pitfalls
Do not use on-demand (situational) dosing as first-line therapy when daily dosing is feasible, as the efficacy difference is substantial and daily treatment produces greater ejaculatory delay. 1, 6
Safety Monitoring
Never abruptly discontinue: Fluoxetine requires gradual tapering to prevent SSRI withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms), particularly given its long half-life of 1-3 days for the parent compound. 5
Screen for serotonergic medications: Avoid combining with MAOIs or other serotonergic drugs due to risk of potentially fatal serotonin syndrome (tremor, hyperreflexia, agitation, diaphoresis, fever). 5, 6
Monitor younger patients: Individuals under age 24 should be closely monitored for suicidal ideation during treatment initiation and dose changes. 5
Adherence Challenges
High dropout rates: Approximately 40% of patients refuse to begin or discontinue treatment within 12 months due to concerns about taking an antidepressant, treatment effects below expectations, cost, and side effects. 6
Long-term compliance is poor: Dropout rates at 6 and 12 months are 56% and 72% respectively, despite significant efficacy. 7
Combination Therapy Considerations
If erectile dysfunction coexists, treat the ED first or concomitantly, as some acquired premature ejaculation may be secondary to erectile dysfunction. 1
Enhanced efficacy with PDE5 inhibitors: Combining fluoxetine with tadalafil produces significantly greater increases in ejaculatory latency (from 49.57 seconds to 336.13 seconds) compared to fluoxetine alone (56.55 to 233.62 seconds) or placebo. 8
Combination therapy option: Daily low-dose SSRI plus on-demand dosing, or SSRI plus PDE5 inhibitor, may be considered for patients with partial response to monotherapy. 1
Comparative Efficacy Among SSRIs
While paroxetine demonstrates the strongest ejaculation delay among SSRIs (8.8-fold increase over baseline), fluoxetine remains highly effective at doses as low as 5 mg/day and is recommended as a first-line option. 1, 5
- Paroxetine has highest sexual dysfunction rates: Paroxetine consistently shows the highest rates of sexual dysfunction among SSRIs, significantly higher than fluoxetine, making fluoxetine a reasonable alternative with better tolerability. 5